PROJECT ABSTRACT: The overall goal of this project is to evaluate novel strategies for identifying genetic variation that contributes to common, complex diseases, with a specific focus on variants that contribute to cardiovascular disease (CVD) risk through parent of origin effects. CVD is the leading cause of death among men and women, and while genome wide association studies (GWAS) have identified some genetic loci that contribute to CVD risk, a lot still remains unknown. The risk alleles identified by GWAS explain little of the heritability of the trait and some of this ?missing heritability? has been attributed to parent of origin effects. I propose to bridge this gap of knowledge by characterizing parent of origin effects on gene expression and on CVD associated phenotypes and calculate parent of origin heritability for CVD phenotypes in the Hutterites. The Hutterites are a founder population of European descent and our group studies a group of ~1400 individuals who descend from 64 founders and are related to each other in a 13 generation pedigree. The Hutterites live communally in the northern plains states and western Canada. With an extended and well recorded pedigree and technological advances in sequencing, we can impute Hutterite genotypes with high accuracy and identify the parent of origin of alleles from 98 Hutterite whole genome sequences to the remaining >1400 individuals in our sample. In addition to gene expression in LCLs and whole blood, we recorded CVD-association phenotypes for a subset of this sample that include measurements of lipids (LDL-c, HDL-c, total cholesterol, triglycerides, and Lp(a)), blood pressure (systolic and diastolic), carotid artery media thickness (CIMT), and echocardiographic traits (left ventricular mass, left atrial volume, among many others), as well as inflammatory cell counts. With this unique population resource, we can disentangle the contribution of maternally inherited alleles and paternally inherited alleles to CVD-associated phenotypes and ultimately to risk for cardiovascular disease.